A Phase 1, Safety and Pharmacokinetic Study of CSL312 in Healthy Subjects
A phase 1, single-centre, randomised, double-blind, placebo-controlled, single ascending dose study to investigate the safety, tolerability and pharmacokinetics of intravenous and subcutaneous CSL312 in healthy subjects.
CSL Limited
48 participants
Oct 28, 2016
Interventional
Conditions
Summary
This is a single centre, randomised, double-blind phase 1 study to assess the safety, tolerability and pharmacokinetics (PK) of single ascending doses of intravenous (IV) or subcutaneous (SC) administrations of CSL312 in healthy subjects. A maximum of 48 subjects will be randomised into this study. Eligible subjects will be enrolled and randomised to receive either CSL312 or placebo. Dosing and initial dose escalation will begin within the IV groups, and upon reaching the third IV cohort, the study will also progress to an SC group. Dose escalation within the IV and SC groups will then progress in parallel with the SC cohorts staggered to start after sentinel dosing in their respective IV cohorts. Blood samples will be collected at various time points for safety, PK and pharmacodynamics (PD) evaluation, and immunogenicity (anti-CSL312 antibodies). Clinical evaluations will include electrocardiograms, vital signs, and physical examinations. Safety follow-up will occur until approximately 84 days after dosing.
Eligibility
Inclusion Criteria4
- Capable of providing written informed consent and willing and able to adhere to all protocol requirements.
- Male aged 18 to 45 years of age at the time of providing written informed consent.
- Judged as healthy by an investigator after completing a comprehensive clinical assessment (detailed medical history and complete physical examination).
- Body mass index (BMI) of 18.0 to less than 30.0 kg/m^2.
Exclusion Criteria5
- Evidence of a clinically significant medical condition, disorder or disease including any of the following: hepatic (hepatitis, cirrhosis); biliary; renal; cardiac; bronchopulmonary; vascular; haematologic; gastrointestinal; allergy; endocrine / metabolic (diabetes, thyroid disorders, adrenal disease); neurologic; psychiatric; immunodeficiency; cancer
- History of clinically significant arterial or venous thrombosis, bleeding disorder, or any abnormal coagulation test result at Screening (confirmed by repeat measurement)
- History of a severe allergic reaction with generalised urticaria; angioedema or anaphylaxis
- Abnormal clinical laboratory values and/or other study assessments, such as vital signs or ECG, deemed clinically significant by the investigator
- Positive serology test result for hepatitis B virus (HBV) surface antigen, human immunodeficiency virus (HIV) antibody, hepatitis A virus (HAV) antibody or hepatitis C virus (HCV) antibody at Screening
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Interventions
This is a single centre, randomised, double-blind phase 1 study to assess the safety, tolerability and pharmacokinetics (PK) of single ascending doses of intravenous (IV) or subcutaneous (SC) administrations of CSL312 in healthy subjects. Subjects can participate in only 1 dose group and will be randomly assigned to receive a single dose of either CSL312 or placebo by IV infusion or SC injection (abdomen). Study drugs will be administered at the study site by study staff. CSL312 is a fully human recombinant anti-FXIIa antibody (Factor XIIa antagonist monoclonal antibody), solution for injection. The dose and infusion volume will be based upon the subject's body weight and the allowable drug concentration. Dose escalation requires Safety Review Committee review of available blinded safety, tolerability, PK and selected Pharmacodynamic (PD) data. Eight groups of 6 subjects are planned; 5 groups for IV administration and 3 groups for SC administration. Dosing and initial dose escalation will begin with the IV groups, and upon reaching the third IV group, the study will progress to the SC groups. Dose escalation within the IV and SC groups will then progress in parallel with the SC groups staggered to start after initial dosing in their respective IV groups. For all IV groups and the first SC group, 2 sentinel subjects per group will be randomised to receive CSL312 or placebo in a 1:1 ratio, and the remaining 4 subjects per group will be randomised to receive CSL312 or placebo in a 3:1 ratio.
Locations(1)
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ACTRN12616001438448